LIGHT, also known as TNFSF14 or CD258, is a member of the TNF superfamily (TNFSF) of ligands. Its name is derived from lymphotoxin-like, exhibits inducible expression and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes. LIGHT is expressed on the surface of T cells upon activation in a tightly regulated manner (Castellano et al. (2002) J. Biol. Chem. 277 42841-51). LIGHT mediates its biological effects by binding one of three TNF superfamily receptors, including the lymphotoxin β receptor (LTβR) (Crowe et al. (1994) Science 264 707-10, Browning et al. (1997) J Immunol 159: 3288-98), the herpes virus entry mediator (HVEM) (Montgomery et al. (1996) Cell 87(3): 427-36), and decoy receptor 3 (DcR3) (Yu et al. (1999) J. Biol. Chem. 274 13733-6). Upon interaction with its receptors, LIGHT exhibits a number of immunostimulatory activities, including regulation of chemokine expression and cell adhesion molecules (Wang, J. et al. (2002) Eur. J. Immunol. 32:1969-1979). For example, LIGHT and LTα1β2 cooperate in lymphoid organogenesis and the development of lymphoid structures (Scheu, S. et al. (2002) J. Exp. Med. 195: 1613-1624; Wang, J. et al. (2002) supra). Signaling of LTβR via a LIGHT transgene has been shown to be sufficient to induce up-regulation of expression of chemokines and adhesion molecules (Wang, J. et al. (2004) J. Clin. Invest. 113: 826-835). LIGHT has also been shown to mediate CD28-independent co-stimulatory activity for T cell priming and expansion, which can lead to enhanced T cell immunity against tumors and/or increased autoimmunity (Tamada, K. et al. (2000) Nat. Med. 6:283-289; Ware, C. F. (2005) Annu. Rev. Immunol. 23:787-819; Wang, J. et al. (2005) J. Immunol. 174:8173-8182).
Given the broad range of immunostimulatory activities associated with LIGHT, the need still exists for identifying novel targeting agents for harnessing these LIGHT-associated activities for the treatment of various hyperproliferative diseases, for example, neoplastic diseases including cancer and metastasis.